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Enrichment of hepatic glycogen and plasma glucose from H₂¹⁸ O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice.

ABSTRACT: Deuterated water (² H₂ O) is a widely used tracer of carbohydrate biosynthesis in both preclinical and clinical settings, but the significant kinetic isotope effects (KIE) of ² H can distort metabolic information and mediate toxicity. ¹⁸ O-water (H₂ ¹⁸ O) has no significant KIE and is incorporated into specific carbohydrate oxygens via well-defined mechanisms, but to date it has not been evaluated in any animal model. Mice were given H₂ ¹⁸ O during overnight feeding and ¹⁸ O-enrichments of liver glycogen, triglyceride glycerol (TG), and blood glucose were quantified by ¹³ C NMR and mass spectrometry (MS). Enrichment of oxygens 5 and 6 relative to body water informed indirect pathway contributions from the Krebs cycle and triose phosphate sources. Compared with mice fed normal chow (NC), mice whose NC was supplemented with a fructose/glucose mix (i.e., a high sugar [HS] diet) had significantly higher indirect pathway contributions from triose phosphate sources, consistent with fructose glycogenesis. Blood glucose and liver TG ¹⁸ O-enrichments were quantified by MS. Blood glucose ¹⁸ O-enrichment was significantly higher for HS versus NC mice and was consistent with gluconeogenic fructose metabolism. TG ¹⁸ O-enrichment was extensive for both NC and HS mice, indicating a high turnover of liver triglyceride, independent of diet. Thus H₂ ¹⁸ O informs hepatic carbohydrate biosynthesis in similar detail to ² H₂ O but without KIE-associated risks.

SUBMITTER: Coelho M

PROVIDER: S-EPMC9845176 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Enrichment of hepatic glycogen and plasma glucose from H₂18 O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice.

Coelho Margarida M Mahar Rohit R Belew Getachew D GD Torres Alejandra A Barosa Cristina C Cabral Fernando F Viegas Ivan I Gastaldelli Amalia A Mendes Vera M VM Manadas Bruno B Jones John G JG Merritt Matthew E ME

NMR in biomedicine 20221022 2

Deuterated water (2 H2 O) is a widely used tracer of carbohydrate biosynthesis in both preclinical and clinical settings, but the significant kinetic isotope effects (KIE) of 2 H can distort metabolic information and mediate toxicity. 18 O-water (H2 18 O) has no significant KIE and is incorporated into specific carbohydrate oxygens via well-defined mechanisms, but to date it has not been evaluated in any animal model. Mice were gi ...[more]

PMID: 36151589

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Dataset Information

Enrichment of hepatic glycogen and plasma glucose from H₂¹⁸ O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice.

Publications

Enrichment of hepatic glycogen and plasma glucose from H₂<sup>18</sup> O informs gluconeogenic and indirect pathway fluxes in naturally feeding mice.

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